NM_004360.5(CDH1):c.1711G>A (p.Gly571Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 10, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000165027.4

Allele description [Variation Report for NM_004360.5(CDH1):c.1711G>A (p.Gly571Ser)]

NM_004360.5(CDH1):c.1711G>A (p.Gly571Ser)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.1711G>A (p.Gly571Ser)

HGVS:

NC_000016.10:g.68819425G>A
NG_008021.1:g.87134G>A
NM_001317184.2:c.1528G>A
NM_001317185.2:c.163G>A
NM_001317186.2:c.-254-2576G>A
NM_004360.5:c.1711G>AMANE SELECT
NP_001304113.1:p.Gly510Ser
NP_001304114.1:p.Gly55Ser
NP_004351.1:p.Gly571Ser
LRG_301t1:c.1711G>A
LRG_301:g.87134G>A
NC_000016.9:g.68853328G>A
NM_004360.3:c.1711G>A
p.G571S
p.Gly571Ser

Protein change:

G510S

Links:

dbSNP: rs786202290

NCBI 1000 Genomes Browser:

rs786202290

Molecular consequence:

NM_001317186.2:c.-254-2576G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317184.2:c.1528G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1711G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000215724	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000215724

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV000215724.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.1711G>A variant (also known as p.G571S), located in coding exon 11 of the CDH1 gene, results from a G to A substitution at nucleotide position 1711. The amino acid change results in glycine to serine at codon 571, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 11, which makes it likely to have some effect on normal mRNA splicing. This alteration has been detected in a family with a clinical history consistent with hereditary diffuse gastric cancer (Ambry internal data). RNA analysis has shown to cause aberrant splicing in patient-derived lymphoblast cells (Casadei S et al. Proc Natl Acad Sci U S A, 2019 Dec;:). This nucleotide position is completely conserved on sequence alignment. This amino acid position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive and direct evidence is insufficient at this time (Ambry internal data). In silico splice site analysis for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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